In this grant application we are proposing extensive studies on the biochemistry of collagen and its biosynthetic precursor, procollagen. The experiments are designed to test the hypothesis that changes in the structure, metabolism, and distribution of genetically distinct collagens in human skin may be associated with the cutaneous aging process. The major emphasis of the present research will be on the isolation, identification, and characterization of the genetically distinct collagens in the human skin. The biochemical characterization will include measurements of the extent of post-translational modifications, such as the hydroxylation o f prolyl and lysyl residues, and the degree of glycosylation. Parallel to the isolation of collagen synthesized in vivo, studies will be performed on human skin fibroblasts in culture. The parameters to be studied include the rate of procollagen synthesis and the characterization of newly synthesized procollagens. To study the changes in collagen during normal aging, skin specimens will be obtained and fibroblast cultures will be initiated from individuals of varying chronological age, and from locations exposed to actinic damage in varying degrees. In studies on accelerated cutaneous aging skin and fibroblast cultures from patients subjected to ultra-violet light for therapeutic purposes, will be examined. The biochemical studies on collagen together with the fibroblast culture studies, correlated with other evidence of cutaneous aging, are expected to lead to significant findings which will give us insight into the understanding of aging processes in general.